This K-08application seeks to further the research career of Ervin R. Fox, MD, MPH, and a cardiologist seeking to expand his research career to include genetic epidemiology and to mature into an independent researcher. He will be sponsored by Thomas H. Mosley, PhD, and Eric Boerwinkle, PhD, both of whom share a long history with several ARIC and GENOA studies. Dr. Fox will also be assisted by an interdisciplinary advisory committee, composed of Christopher Friedrich, MD, PhD;John Hall, PhD;Herman Taylor, MD, MPH;and James Wilson, MD. Several training initiatives to further Dr. Fox's career as an independent researcher have been identified, including completion of formal coursework in genetic epidemiology at Tulane University and summer courses at Washington University, Johns Hopkins University and Jackson Laboratory in Maine. Cardiac disease, including myocardial infarction, hypertensive and ischemic heart disease, and heart failure, is the leading cause of mortality and morbidity, accounting for 28% of the 2.4 million deaths in the U.S. each year. African-Americans suffer a disproportionate burden from cardiac disease. Dr. Fox's proposed study will take advantage of extant resources of the Genetic Epidemiology Network of Arteriopathy (GENOA) study, part of the Family Blood Pressure Program, to examine the contribution of novel risk factors and genes to left ventricular (LV) structure and function in a population-based cohort of hypertensive African- American sibships from the GENOA Jackson Field Center. The scope of research planned for the candidate consists of the following specific aims: Determine whether novel risk factors are associated with LV structure and function in African-American siblings from the GENOA Jackson Field Center;Determine whether any of 387 highly polymorphic tandem repeat marker loci spanning the genome are linked to genes influencing LV structure and function in African-American siblings from the GENOA Jackson Field Center;and Determine whether polymorphisms in candidate genes in the adrenergic-receptor pathway are associated with LV structure and function in African-American siblings from the GENOA Jackson Field Center. (End of Abstract)